{"doi":"10.1073/pnas.1419669112","title":"Up-regulation of lysosomal TRPML1 channels is essential for lysosomal adaptation to nutrient starvation","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>\n                    Lysosomes are the cell’s degradation center. To adapt to different environmental conditions, the cell has evolved a set of delicate mechanisms to rapidly change lysosome function, which is referred to as lysosomal adaptation. Notably, lysosomal adaptation is required for cell survival under low nutrient conditions. In this study, we identified TRPML1, a lysosomal Ca\n                    <jats:sup>2+</jats:sup>\n                    -permeant ion channel, as an essential player required for lysosomal adaptation. The activity of TRPML1 is potently (up to 10-fold) and rapidly increased upon nutrient starvation. Furthermore, pharmacological inhibition or genetic deletion of TRPML1 completely abolished the effects of starvation on boosting the degradation capability of lysosomes.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2015,"id":643942,"datarank":0.8300084233091282,"base_score":5.53338948872752,"endowment":5.53338948872752,"self_citation_contribution":0.8300084233091282,"citation_network_contribution":0.0,"self_endowment_contribution":0.8300084233091282,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":252,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1040048,"name":"Qiong Gao","orcid":"0000-0002-0406-1594","position":1,"is_corresponding":false},{"id":1531605,"name":"Meimei Yang","orcid":null,"position":2,"is_corresponding":false},{"id":1160368,"name":"Xiaoli Zhang","orcid":"0009-0004-4269-4685","position":3,"is_corresponding":false},{"id":1293524,"name":"Lu Yu","orcid":"0000-0002-2110-9019","position":4,"is_corresponding":false},{"id":519870,"name":"Maria Lawas","orcid":null,"position":5,"is_corresponding":false},{"id":1174099,"name":"Xinran Li","orcid":"0000-0001-8988-7223","position":6,"is_corresponding":false},{"id":1675766,"name":"Marthe Bryant-Genevier","orcid":null,"position":7,"is_corresponding":false},{"id":1675767,"name":"Noel T. Southall","orcid":null,"position":8,"is_corresponding":false},{"id":505883,"name":"Juan Marugan","orcid":null,"position":9,"is_corresponding":false},{"id":228425,"name":"Marc Ferrer","orcid":"0000-0003-4569-9137","position":10,"is_corresponding":false},{"id":254906,"name":"Haoxing Xu","orcid":"0000-0003-3561-4654","position":11,"is_corresponding":false},{"id":1675765,"name":"Wuyang Wang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Up-regulation of lysosomal TRPML1 channels is essential for lysosomal adaptation to nutrient starvation","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>\n                    Lysosomes are the cell’s degradation center. To adapt to different environmental conditions, the cell has evolved a set of delicate mechanisms to rapidly change lysosome function, which is referred to as lysosomal adaptation. Notably, lysosomal adaptation is required for cell survival under low nutrient conditions. In this study, we identified TRPML1, a lysosomal Ca\n                    <jats:sup>2+</jats:sup>\n                    -permeant ion channel, as an essential player required for lysosomal adaptation. The activity of TRPML1 is potently (up to 10-fold) and rapidly increased upon nutrient starvation. Furthermore, pharmacological inhibition or genetic deletion of TRPML1 completely abolished the effects of starvation on boosting the degradation capability of lysosomes.\n                  </jats:p>","is_dataset_classified":null,"base_score":5.53338948872752,"endowment":5.53338948872752,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25733853","pmcid":"PMC4371935","openalex_id":"https://openalex.org/W2060602529","authors":[],"funders":[{"funder_name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","grant_id":"AR060837","title":null},{"funder_name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","grant_id":"NS062792","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"MH096595","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS062792","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"R03 MH096595","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01 AR060837","title":null}],"total_grants":6,"fwci":14.2863,"citation_percentile":0.99418886,"influential_citations":0,"citation_trend":[{"year":2015,"count":2},{"year":2016,"count":18},{"year":2017,"count":19},{"year":2018,"count":18},{"year":2019,"count":20},{"year":2020,"count":26},{"year":2021,"count":35},{"year":2022,"count":24},{"year":2023,"count":27},{"year":2024,"count":36},{"year":2025,"count":19},{"year":2026,"count":8}],"oa_status":"bronze","license":"http://www.pnas.org/site/misc/userlicense.xhtml","oa_locations":[{"url":"https://www.pnas.org/content/pnas/112/11/E1373.full.pdf","host_type":"journal"},{"url":"https://www.pnas.org/content/pnas/112/11/E1373.full.pdf","host_type":"publisher"},{"url":"http://www.pnas.org/syndication/doi/10.1073/pnas.1419669112","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1419669112","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1419669112","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25733853","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4371935","host_type":"repository"}],"fields_of_study":["Calcium signaling and nucleotide metabolism","Plant Molecular Biology Research","Plant Stress Responses and Tolerance","Amino Acids","Animals","Basic Helix-Loop-Helix Leucine Zipper Transcription Factors","Calcium","Cell Line","Cell Nucleus","Cholesterol","Gene Expression Regulation","Humans","Lysosomes","Mutation","Niemann-Pick Diseases","Phosphatidylinositol Phosphates","Protein Biosynthesis","Protein Transport","Proteolysis","Sodium","TOR Serine-Threonine Kinases","Transcription, Genetic","Transient Receptor Potential Channels","Up-Regulation"],"mesh_terms":["Amino Acids","Animals","Calcium","Cell Line","Cell Nucleus","Cholesterol","Gene Expression Regulation","Humans","Lysosomes","Mutation","Niemann-Pick Diseases","Sodium","Transcription, Genetic","Protein Biosynthesis","Up-Regulation","Phosphatidylinositol Phosphates","Protein Transport","Transient Receptor Potential Channels","Basic Helix-Loop-Helix Leucine Zipper Transcription Factors","TOR Serine-Threonine Kinases","Proteolysis"],"keywords":["Lysosome","Cell biology","Starvation","Biology","Adaptation (eye)","Biochemistry","Chemistry","Enzyme","Endocrinology","Neuroscience","Mtor","Tfeb","Trpml1"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-08T19:54:19.932342Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}